title: EcxAB is a founding member of a new family of metalloprotease AB5 toxins with a hybrid cholera-like B subunit.
abstract: AB5 toxins are composed of an enzymatic A subunit that disrupts cellular function associated with a pentameric B subunit required for host cell invasion. EcxAB is an AB5 toxin isolated from clinical strains of Escherichia coli classified as part of the cholera family due to B subunit homology. Cholera-group toxins have catalytic ADP-ribosyltransferases as their A subunits, so it was surprising that EcxA did not. We confirmed that EcxAB self-associates as a functional toxin and obtained its structure. EcxAB is a prototypical member of a hybrid AB5 toxin family containing metzincin-type metalloproteases as their active A subunit paired to a cholera-like B subunit. Furthermore, EcxA is distinct from previously characterized proteases and thus founds an AB5-associated metzincin family that we term the toxilysins. EcxAB provides the first observation of conserved B subunit usage across different AB5 toxin families and provides evidence that the intersubunit interface of these toxins is far more permissive than previously supposed.
authors.affiliation: ARC Centre of Excellence in Structural and Functional Microbial Genomics, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Natasha M
authors.initials: NM
authors.lastname: Ng
authors.forename: Dene R
authors.initials: DR
authors.lastname: Littler
authors.forename: Adrienne W
authors.initials: AW
authors.lastname: Paton
authors.forename: Jérôme
authors.initials: J
authors.lastname: Le Nours
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.forename: Travis
authors.initials: T
authors.lastname: Beddoe
mesh_terms: D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D020134:Catalytic Domain; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000737:chemistry*; D006860:Hydrogen Bonding; D045726:Metalloproteases / Q000737:chemistry*; D008958:Models, Molecular; D011134:Polysaccharides / Q000737:chemistry; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry; D014709:Vero Cells
chemical_list: D029968:Escherichia coli Proteins; D011134:Polysaccharides; D021122:Protein Subunits; C000588981:EcxA proetin, E coli; C000588982:EcxB protein, E coli; D045726:Metalloproteases